The World Health Organization estimates that AIDS has killed more than 25 million people since it was first recognized. In 2007 there were 2.7 million new HIV infections and 2 million HIV-related deaths. Many chronic viral infections are caused by retroviruses. For certain chronic viral infections, the immune system cannot clear the virus from the host even with the aid of therapeutic agents. For example, although highly active anti-retroviral therapy (HAART) may improve symptoms associated with infection, there is currently no cure for HIV or vaccine, and methods of preventing infections would be desirable.
Recombinant modified vaccinia virus Ankara (MVA) expressing SIV or HIV Gag-Pol and Env was described for managing immunodeficiency virus infections in nonhuman primates. Wyatt et al., (2004) AIDS Res Hum Retroviruses 20(6):645-53. This vaccine elicits a good CD4 T-cell response but a relatively weak CD8 T-cell response. It is desirable to improve the ability of the vaccine to elicit a stronger CD8 response since CD4 cells are preferentially infected by the HIV virus.
Clinical trials using CD40L to induce immune responses has been described. Tahara et al., (2004) Nat Med 10:835-841. Insertion of the CD40L gene into the transcription units of replication incompetent adenoviral vectors has been reported. Wierda et al., (2000) Blood 96:2917-2924. A chimeric molecule composed of a target antigen linked to the extracellular domain (ecd) of the CD40L has been described. Tang et al., (2009) Cancer Immunol Immunother 58(12):1949-57.